To add to the slew of data that recently surfaced regarding Sanofi-Aventis’ dronedarone (Multaq) and its potential to cause cardiovascular events in permanent atrial fibrillation (AF) patients during the PALLAS trial, the European Society of Cardiology (ESC) says that it will update its AF guidelines.
Current ESC guidelines for the treatment of AF recommend dronedarone to prevent AF recurrence and reduce the ventricular rate in non-permanent AF. ESC advises against administration of dronedarone to NYHA Class III or IV patients or those with decompensated heart failure.
The ESC guidelines coincide with FDA and European Medicines Agency (EMA) guidelines that also advise that the drug be restricted to the aforementioned indications and not be administered to permanent AF patients.
The statement was released after both EMA and FDA expressed concern with dronedarone after the PALLAS trial, a Phase IIIb clinical trial comparing the efficacy of a 400 mg twice-daily dose of dronedarone. The trial was halted after researchers found an increase in cardiovascular events in the dronedarone arm when administered to permanent AF patients.
"The ESC is aware of the early termination of the PALLAS trial (a randomized dronedarone versus placebo outcomes study in patients with permanent atrial fibrillation and cardiovascular risk) because of adverse outcomes associated with dronedarone,” according to the ESC statement.
An FDA review found that permanent AF patients administered dronedarone saw a two-fold increase in mortality and three-fold increase in stroke and hospitalizations.
As the FDA and EMA continue conducting risk-benefit reviews of the drug, ESC said that it will update AF guidelines when the final results of the PALLAS trial are published and regulatory bodies revise dronedarone’s label.
“The focused update of the AF guidelines will also allow the incorporation of formal recommendations relating to the use of vernakalant, one or more of the new anticoagulant agents that are alternatives to warfarin, and left atrial appendage closure devices,” the ESC said.
Earlier this year dronedarone was under increased scrutiny when two cases surfaced where patients taking dronedarone suffered acute liver failure, which led to liver transplants. As a result, the FDA and the EU slapped warning labels on dronedarone.
The ESC also has advised patients who are currently administered dronedarone to continue therapy and consult their physician with any concerns.